The goal of this study is to develop and evaluate advanced annular-array transducer technology for rapid, high-definition imaging in significant medical-research applications. The study will assess high frequency ultrasound (HFU, = 20 MHz) annular arrays in two important applications: 1) imaging microstructure in small animals (e.g., mouse embryos); and 2) imaging posterior vitreous detachments (PVDs) associated with diabetic retinopathy, the leading cause of blindness in the US working-age population according to Prevent Blindness America. Current HFU instruments do not use linear arrays for such applications because of a variety of technical and cost reasons. Instead, current HFU instruments use mechanically scanned, single-element transducers, which provide fine-resolution images over a very limited depth of field (DOF). For small-animal applications, a shallow DOF causes most anatomical boundaries in the specimen to be poorly defined; therefore, accurate micro-structural and volumetric analyses are nearly impossible. For ophthalmic applications, a shallow DOF causes most ocular anatomy to be imaged with poor definition compared to the in-focus region; therefore, because only a small portion of the eye is in focus at a given time, detection and assessment of ocular conditions such as PVD are prone to inaccuracies and false-negative determinations. Annular-array transducers offer a promising approach to significantly extend DOF and to increase the depth range over which fine-lateral resolution is provided. This proposal seeks to continue the HFU annular-array studies initiated under grant EY014371 that demonstrated the improved imaging capability of synthetically-focused annular arrays using in vivo rabbit eyes, in vivo mouse embryos, and human eye-bank eyes. The proposed project will extend those previous studies by developing and validating a real-time HFU, annular-array-based, rapid-imaging system capable of 1) dynamic-receive display imaging at a rate of > 10 fps; 2) data acquisition in < 0.2 s for single-frame, synthetically-focused imaging; and 3) 3D data collection in < 20 s. The proposed system will be modular to facilitate upgrading system components and features. We will validate system performance using animal experiments and human-subject examinations. First, in vivo animal experiments will be conducted with rabbit eyes to evaluate a 40-MHz annular array for anterior-segment imaging and a 20-MHz annular array for posterior segment and full-globe imaging. We also will utilize the 40-MHz annular array to perform in vivo 3D imaging and volumetric segmentation studies with mouse embryos. Second, we will test the hypothesis that 20-MHz annular arrays improve detection of PVD. Validation of this hypothesis will significantly improve our ability to assess disease status in diabetic retinopathy. [unreadable] [unreadable] [unreadable]